title: Mutations in the gene encoding CADM1 are associated with autism spectrum disorder.
abstract: The unified idea on the molecular pathogenesis of Autism Spectrum Disorder (ASD) is still unknown although mutations in genes encoding neuroligins and SHANK3 have been shown in a small part of the patients. RA175/SynCAM1/CADM1(CADM1), a member of immunoglobulin superfamily, is another synaptic cell adhesion molecule. To clarify the idea that impaired synaptogenesis underlies the pathogenesis of ASD, we examined the relationship between mutations in the CADM1 gene and ASD. We found two missense mutations, C739A(H246N) and A755C(Y251S), in the CADM1 gene of male Caucasian ASD patients and their family members. Both mutations were located in the third immunoglobulin domain, which is essential for trans-active interaction. The mutated CADM1 exhibited less amount of high molecular weight with the matured oligosaccharide, defective trafficking to the cell surface, and more susceptibility to the cleavage and or degradation. Our findings provide key support for the unified idea that impaired synaptogenesis underlies the pathogenesis of ASD.
authors.affiliation: Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi 329-0498, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhiling
authors.forename: Eriko
authors.initials: E
authors.lastname: Fujita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
authors.forename: Takashi
authors.initials: T
authors.lastname: Momoi
authors.forename: Mariko Y
authors.initials: MY
authors.lastname: Momoi
mesh_terms: D000595:Amino Acid Sequence; D001321:Autistic Disorder / Q000235:genetics*; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins